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E-GEOD-49356 - Homeobox protein NKX2-3 modulates lymphocyte dynamics and promotes B-cell lymphomagenesis

Status
Released on 22 July 2016, last updated on 31 July 2016
Organism
Mus musculus
Samples (20)
Array (1)
Protocols (7)
Description
Molecular cloning of a t(10;14)(q24;q32) from a B-cell lymphoma showed a recurrent breakpoint in homeobox NKX2-3 gene, which was highly expressed in comparison to non-expressing mature B lymphocytes. Epigenetically-mediated NKX2-3 over-expression was selectively found in patients with splenic marginal-zone lymphoma, MALT lymphoma and extranodal diffuse large-cell lymphoma. In young mice, restricted expression of NKX2-3 to lymphocytes activated multiple integrins (LFA-1, VLA-4, MAC-1), adhesion molecules (ICAM-1, MadCAM-1, L-selectin) and the chemokine receptor CXCR4 that enhanced their homing and migration to splenic tissues, whereby they were retained, progressively accumulating to form non-clonal tumors. At 18 months, B cells acquired genomic rearrangements and generated clonal B-cell lymphomas mirroring the spectrum of human NKX2-3-expressing tumors. Mouse and human lymphomas displaying NKX2-3 expression shared histopahological, genomic and molecular features, including canonical NF-KB activation. NF-KB inhibition reduced tumorigenecity of NKX2-3-positive lymphomas. Our study reveals that oncogenic NKX2-3 promotes B-cell lymphomagenesis by disturbing lymphocyte dynamics. Comparisson of global gene expression profiling between Emu-NKX2-3 transgenes mice and wild type mice.
Experiment type
transcription profiling by array 
Contacts
Victor Segura <vsegura@unav.es>, Eloy F Robles, Jose A Martinez-Climent
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-49356.idf.txt
Sample and data relationshipE-GEOD-49356.sdrf.txt
Raw data (1)E-GEOD-49356.raw.1.zip
Processed data (1)E-GEOD-49356.processed.1.zip
Array designA-AFFY-130.adf.txt
Links